The effect of tyrosine-deficient total parenteral nutrition on the synthesis of dihydroxyphenylalanine in neural tissue and the activities of tyrosine and branched-chain aminotransferases.
The poor solubility of tyrosine (Tyr) limits the amount of this amino acid in total parenteral nutrition (TPN). In rats maintained on a standard pediatric TPN mixture, plasma and brain concentrations of Tyr are reduced to about 25% of the levels in chow-fed controls. To determine whether these low concentrations of Tyr affect the synthesis of catecholamines in neural tissue, the rate-limiting step (conversion of Tyr to dihydroxyphenylalanine [DOPA]) is studied by administering NSD-1015 to block the pyridoxal phosphate (PLP)-dependent decarboxylation of DOPA. However, in TPN rats, plasma concentrations of Tyr are increased by drug treatment. Because brain Tyr is also increased, these and other experiments using NSD-1015 clearly overestimate the rate of DOPA synthesis for drug-free rats on TPN. Nevertheless, in TPN rats, there is less DOPA in the brain in one experiment and less DOPA in the olfactory bulbs in another, versus control rats. Further examination of the metabolic effects of NSD-1015 reveals that the drug also elevates the concentration of branched-chain amino acids (BCAAs) in the plasma of TPN rats. These findings result from inhibition by NSD-1015 of the PLP-dependent aminotransferases that initiate catabolism of Tyr in the liver and BCAAs in the muscle. Despite the pronounced reduction in plasma Tyr, TPN rats showed a marked increase in the activity of hepatic Tyr aminotransferase compared with chow-fed controls. Conversely, although TPN elevates BCAA concentrations in plasma, the activity of branched-chain aminotransferase (BCAT) in the heart muscle of TPN rats is not different from control values. Different values but the same relationships are seen in drug-free rats.
Hilton
M A
MA
Department of Biochemistry and Molecular Biology, School of Medicine, University of Louisville, KY 40292, USA.
Fonda
M L
ML
Hilton
F K
FK
D000597:Amino Acids, Branched-Chain / Q000097:blood; D000818:Animals; D001921:Brain / Q000378:metabolism*; D004295:Dihydroxyphenylalanine / Q000096:biosynthesis*; D006834:Hydrazines / Q000494:pharmacology; D008297:Male; D010289:Parenteral Nutrition, Total; D051381:Rats; D017207:Rats, Sprague-Dawley; D000637:Transaminases / Q000378:metabolism*; D014443:Tyrosine / Q000172:deficiency*; D014444:Tyrosine Transaminase / Q000378:metabolism*
D000597:Amino Acids, Branched-Chain; D006834:Hydrazines; D014443:Tyrosine; D004295:Dihydroxyphenylalanine; C004297:3-hydroxybenzylhydrazine; D000637:Transaminases; C019798:branched-chain-amino-acid transaminase; D014444:Tyrosine Transaminase